Adoptive Transfer of EBV Specific CD8+ T Cell Clones Can Transiently Control EBV Infection in Humanized Mice |
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| Authors: | Olga Antsiferova Anne Müller Patrick C R?mer Obinna Chijioke Bithi Chatterjee Ana Raykova Raquel Planas Mireia Sospedra Anatoliy Shumilov Ming-Han Tsai Henri-Jacques Delecluse Christian Münz |
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| Institution: | 1. Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.; 2. Neuroimmunology and Multiple Sclerosis Research, Department of Neurology, University Hospital Zürich, Zürich, Switzerland.; 3. Division of Pathogenesis of Virus Associated Tumors, German Cancer Research Centre (DKFZ), Heidelberg, Germany.; University of Southern California Keck School of Medicine, United States of America, |
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| Abstract: | Epstein Barr virus (EBV) infection expands CD8+ T cells specific for lytic antigens to high frequencies during symptomatic primary infection, and maintains these at significant numbers during persistence. Despite this, the protective function of these lytic EBV antigen-specific cytotoxic CD8+ T cells remains unclear. Here we demonstrate that lytic EBV replication does not significantly contribute to virus-induced B cell proliferation in vitro and in vivo in a mouse model with reconstituted human immune system components (huNSG mice). However, we report a trend to reduction of EBV-induced lymphoproliferation outside of lymphoid organs upon diminished lytic replication. Moreover, we could demonstrate that CD8+ T cells against the lytic EBV antigen BMLF1 can eliminate lytically replicating EBV-transformed B cells from lymphoblastoid cell lines (LCLs) and in vivo, thereby transiently controlling high viremia after adoptive transfer into EBV infected huNSG mice. These findings suggest a protective function for lytic EBV antigen-specific CD8+ T cells against EBV infection and against virus-associated tumors in extra-lymphoid organs. These specificities should be explored for EBV-specific vaccine development. |
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